This project was initiated this year due to the multidisciplinary interest of various investigators at NIEHS. Over the last few years, interactions between the immune system and the nervous system have become well established if not yet understood. These interactions may be direct, indirect, via the Hypothalamic-Pituitary-Adrenal Axis or vis the resident immune cells of the brain. There have been a number of proposed links between the immune system and the nervous system (and possible interactions with the reproductive system) including: 1) prolonged post-natal development/maturation of both systems. 2) infection in the pregnant mother and possible transfer of infection to the offspring or the transfer of factors of the pro-inflammatory cascade (TNFalpha, Interleukin-6) to the offspring and long-term effects on the child as related to an immune-mediated response. 3) the transfer of active virsus into the brain (e.g., Herpes, HIV, West-Nile) and the manifestation of cognitive deficits/dementia. 4) the increased occurrance of cognitive deficits in human cases related to autoimmune disease (e.g., AIDs, Multiple Sclerosis, Tryptophan-induced autoimmunity), 5) the lack of success with therapeutic intervention with anti-inflammatory agents for cognitive impairment suggesting a more complicated interactions between the systems than previously anticipated. Within the framework of exposure to environmental agents, there exists a substantial data base to suggest that acute responses of the immune system can occur as a result of chemical exposure. Additional efforts are underway within NIEHS to generate such information of the developing immune system. Quite often, the agents or factors that have the capacity to alter the immune system are shown to also alter the nervous system. Thus, it is the purpose of this project to attempt to identify interactions between the two systems that may contribute not only to acute adverse effects but also to long-term adverse outcomes.